Millis resident William Vogt, a senior mechanical engineering student at the University of Massachusetts Amherst, is using a tried and true engineering discipline, called “control theory,” to give medical doctors a better way to regulate a life-enhancing medication for kidney patients. The medication is recombinant erythropoietin (rhEPO), which stimulates the failing production of red blood cells in kidney patients, but is currently very difficult to regulate effectively. What Vogt is developing through methods used in engineering control theory is a simple formula by which doctors can easily calculate a very precise schedule of rhEPO doses that is specific to any individual kidney patient and will manage his or her red blood cell production in the healthiest possible way.

“Our protocol would allow doctors to give patients the proper dosage of rhEPO that produces a beneficial red blood cell level without taking it too high,” explains Vogt. “And it would also reach that target in a healthy span of time, neither too quickly nor too slowly. The ideal would be a simple equation, without needing any special software, which would give doctors the proper dosage and how often it should be applied.”

One of the functions of the kidney is to regulate the production of red blood cells, which are vital because they serve as oxygen transporters for all the organs and tissues of the body. The kidney secretes a hormone called erythropoietin, EPO for short, which regulates how humans make red blood cells and maintains a healthy balance between oxygen supply and demand. As kidneys grow dysfunctional, EPO production is one of the important functions that deteriorate.

In response, doctors prescribe doses of rhEPO, the artificial form of EPO and the standard treatment for anemia in kidney patients. Unfortunately, setting the dosage depends largely on trial and error. After estimating the dose and its frequency, the doctor must then assess the results by measuring biomarkers such as hemoglobin level (the oxygen-transporting protein in red blood cells) or red blood cell count to see how the patient is responding. What Vogt is working on is a more precise method of determining these doses.

When trying to regulate the red blood cell count in this way, doctors without knowing it are serving as what engineers refer to as a “feedback controller” in a closed loop system. In control theory, a controller is a device that monitors and affects the operational conditions of a given dynamical system. For example, in the heating system of a house, the thermostat is the feedback controller for sensing air temperature and regulating the furnace if it goes too high or low.

Similar to thermostats, doctors are the feedback controllers regulating red blood cell counts in kidney patients through doses of rhEPO. The problem here is that the dosages can easily leave the blood counts either too low, which results in anemia, or too high, which increases the mortality risk for kidney patients because the production of red blood cells can shut down. What’s more, fast swings in red cell blood count are also dangerous for patients.

“The blood cell system is very large, and if you shake it too much, that’s not good for your body because it has to adjust and change how it’s operating,” says Vogt about changing the blood count too quickly. “So what we would like to see ideally is bringing the red blood cell count gradually to the target level without going over it. If the body were a martini, we want it stirred not shaken.”

Vogt is trying to apply classic engineering techniques to this medical problem and produce a protocol for determining an exact schedule of precise EPO doses that keeps kidney patients as healthy as possible.

“The protocol is the ultimate goal,” says Vogt. “We’d like to design something simple for the doctors to use. We want to design a simple controller in our mechanical engineering world that can be translated quite easily into an empirical calculation that a doctor can do.”

Vogt is working on a research team composed of Professor Yossi Chait of the Mechanical and Industrial Engineering (MIE) Department, Christopher Hollot, head of the Electrical and Computer Engineering Department, Joseph Horowitz from the Department of Mathematics and Statistics, Michael Germain, an MD from Bay State Health Systems, and MIE graduate student Rajiv Shrestha. Vogt is receiving his patient data from the records of 50 kidney patients at Bay State Medical Center in Springfield. His goal is a very precise dosage protocol that can be applied to all 50 patients and any other kidney patient.

“We’re just starting to crunch the data and see what they look like,” says Vogt. “We want a model that works pretty well for everyone.”

The model being used by Vogt to create this dosage protocol could conceivably be applied to many other medical dosage problems in the healthcare field.

“So instead of entering data from the red blood cell producing system,” says Vogt, “it could be some kind of chemotherapy dosage protocol. From an engineering perspective we know that a closed loop system like the human body is intrinsically a system that can be analyzed by control theory. It’s very straightforward.” (February 2009)